The goals of this project are to characterize lymphocyte FcGamma receptors genetically and functionally. Previous findings indicate that the FcGamma receptors of B lymphocytes interact with: a) the lymphocyte cytoskeleton, b) Ia antigens and Lym antigens, c) surface IgM, and d) surface IgD. Each of these interactions is distinct, specific, and non-random. Recently monoclonal antibodies specific for FcGammaR have been shown to induce B lymphocytes to both proliferate and secrete antibody (function). This response does not require T lymphocytes or accessory cells and is specific by a variety of criteria. This is the only antibody specific for a B lymphocyte receptor which triggers function. The monoclonal anti-FcGammaR antibody stimulates primarily a subset of B lymphocytes characterized by increased size and the presence of the marker LyB5. It also triggers B lymphocytes to antibody secretion in vivo. These findings strongly suggest that B lymphocyte FcGamma receptors are central to B lymphocyte activation and immunoregulation. Finally, preliminary studies indicate that the monoclonal anti-FcGammaR antibodies stimulate natural killer cell activity in vitro.